Glenn Morton wrote (Fri, 22 Sep 2000 18:11:13 -0500 (CDT), Random chance
brings meaning, in part):
>>> It is NOT cheating when the main point was that when people say that random sequences can't produce meaning it is clear from these examples, NO MATTER HOW RARE THE PHENOMENON, that meaning is generated from two random sequences. Just because there is randomness in a system doesn't mean that it can't produce meaning. While much discussion has proceeded, that simple fact was my main point. Randomness does not preclude meaning or semantics. <<<
Glenn:
You are right, there IS randomness in all these 21-letter sequences, no
matter whether they were generated by encrypting a meaningful phrase or
by running a random number generator, and ANY meaningful 21-letter
message can be generated from ANY of the 26^21 possible sequences if the
right key is found.
But this fact does NOT imply that meaning or semantics can arise
spontaneously by random processes, without some intelligent input of
information. Either this happens when the sender encrypts his message
and gives the key to the designated receiver, or when an eavesdropper
searches for meaning, using very much intelligence and effort in the
process.
Do such encrypted messages really tell us anything about the process of
evolution? There, we have a random number generator alright, and we have
natural selection. But for finding meaning, natural selection isn't as
patient and powerful as an intelligent cryptographer with his computer.
In the evolutionary process, the only possible natural source of
information is the environment. But the extraction of this information
is extremely slow, probably only a fraction of a bit per generation -
when any useful mutants are available at all. And if they are, they must
penetrate the entire population before being fixed. For small selective
advantages and large populations, the mutation still risks being lost by
random drift.
If we compare this process with the huge amount of information in
today's biosphere, I'm pretty sure 4 billion years is by far too little
time. It is estimated that about 1000 different protein folds exist in
living organisms, comprising about 5000 different protein families (Wolf
Y.I., Grishin N.V., Koonin E.V. "Estimating the number of protein folds
and families from complete genome data", J.Molec.Biol. 299 (2000),
897-905). When we compare the prebiotic Earth with today's biosphere as
a whole, each of these folds, families and individual proteins with
their functions had to arise at least once somewhere. There is NO
evidence that all or most of them could be derived from one or a few
initial sequences through step-by-step mutation, each of the
intermediates being positively selected, and this within a few billion
years.
In my post, I was discussing the evolution of functional proteins in a
DNA-RNA-protein world, not evolution in an RNA world. I never talked
about ribozymes (I did mention ribonucleases, but these are protein
enzymes). I know about the in vitro selection of functional ribozymes,
but I do not consider these as valid models of evolution at all. They
just are techniques for finding active ribozymes among as many sequences
as possible. Of course, mutagenizing steps generate new diversity, but
the selection procedures most certainly are NOT natural. What we can
learn from some of these experiments is the frequency of a given
ribozyme activity among the pool of RNA sequences supplied (which
usually is just a very tiny sample of all possible sequences, and of
unknown bias).
Further problems of the ribozyme work are: (1) Usually artificial
"evolution" tapers off at activities several orders of magnitude lower
than natural ribozymes (not to speak of protein enzymes) (cf. Bartel &
Szostak, Science 261, 1411). (2) We don't yet know whether there ever
was an RNA world. (3) We don't know whether it would be viable at all.
(4) We don't know how it could have arisen by natural processes. Leslie
E. Orgel, one of the pioneers in this field, wrote (Trends Bioch.Sci. 23
(1998), 491):
"There are three main contending theories of the prebiotic origin of
biomonomers [1. strongly reducing primitive atmosphere, 2. meteorites,
3. deep-sea vents]. No theory is compelling, and none can be rejected
out of hand ... The situation with regard to the evolution of a
self-replicating system is less satisfactory; there are at least as many
suspects, but there are virtually no experimental data ... [There is] a
very large gap between the complexity of molecules that are readily
synthesized in simulations of the [suspected] chemistry of the early
earth and the molecules that are known to form potentially replicating
informational structures ... Several alternative scenarios might account
for the self-organization of a self-replicating entity from prebiotic
organic material, but all of those that are well formulated are based on
hypothetical chemical syntheses that are problematic ... I have
neglected important aspects of prebiotic chemistry (e.g. the origin of
chirality, the organic chemistry of solar bodies other than the earth,
and the formation of membranes) ... There is no basis in known chemistry
for the belief that long sequences of reactions can organize
spontaneously - and every reason to believe that they cannot."
Against this background, I think it is moot, at present, to speculate
about the probabilities of evolutionary steps in an RNA world. We DO
know, on the other hand, how the microevolutionary mechanisms work in
our world. This is why I chose to deal with this only, rather than with
ribozymes.
You are right in pointing out that Yockey revised his probability
estimate for cytochrome c (now iso-1-cytochrome c) in his book
"Information theory and molecular biology" (Cambridge: Cambridge
Univ.Press, 1992). On p.254, he gives the probability of accidentally
finding any one of the presumably active iso-1-cytochromes c as 2 x
10^(-44), which is 21 orders of magnitude better than his 1977 estimate
for cytochrome c. But I think most of this difference is NOT due to new
experimental evidence (e.g. new sequences), but to his refined
calculating method, taking into account adjusted probabilities for the
individual amino acids, to find their "effective number", so it is
hardly likely that this new estimate will increase any more. As 10^(-44)
is still much too low to be of any use, I didn't think it worth while to
try to present his much more complicated new procedure.
One problem which remains is his assumption that there are no
interdependencies between the different amino acid occupations within
the sequence. On p.141, he even cites one observed case where the
equivalence prediction of his procedure fails. We don't know how many
more there are. Such interdependencies would reduce the overall
probability massively.
Furthermore, Yockey deals with modern cytochromes c (and some artificial
derivatives) only, which are the result of a few billion years of
optimization. A "primitive" enzyme may be more easily accessible. The
only reason I quoted him was that we have NO information about ANY
"primitive" enzyme.
The important point is to find cases where natural selection does NOT
work (yet), because then only we can do meaningful probability
calculations, which apply only to random walks without selection of
intermediate steps. The case I considered was the origin of a new
enzymatic activity which did not exist before (anywhere in the
biosphere, e.g. a new one of those 1000 folds, and using wildly
over-optimistic assumptions). As soon as a minimal activity has arisen,
natural selection can attack and speed up evolution by unknown amounts.
This is another reason why the artificial ribozyme selection experiments
are irrelevant in this connection.
By the way, I would still be very interested to hear any comments about
the model I calculated, from you, Glenn, or anyone else!
In both of the cases you quote, an initial catalytic activity of the
type selected for was present initially (gamma-thiophosphate transfer in
Lorsch J.R., Szostak J.W., Nature 371 (1994), 31, and
oligoribonucleotide linkage in Bartel D.P., Szostak J.W., Science 261
(1993), 1411), and the same applies, as far as I know, to all other in
vitro ribozyme selection experiments done to date.
Thus, on both counts, random-path mutagenization to generate a
previously non-existing activity and natural vs. intelligent selection,
in vitro ribozyme selection experiments are NOT valid models of the
crucial steps in darwinian evolution, and the artificial ribozyme
figures of 10^(-16) or 10^(-13) are irrelevant. The apocryphal joke
about a horse's teeth is therefore quite inappropriate. We do NOT
dispose af ANY experimental or observational data about these critical
steps which would indicate whether macroevolution by natural means alone
is plausible or not - even quite apart from the origin of life itself.
Peter Rüst
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